TRPV6 channel mediates alcohol-induced gut barrier dysfunction and systemic response.

ABSTRACT: Intestinal epithelial tight junction disruption is a primary contributing factor in alcohol-associated endotoxemia, systemic inflammation, and multiple organ damage. Ethanol and acetaldehyde disrupt tight junctions by elevating intracellular Ca²⁺. Here we identify TRPV6, a Ca²⁺-permeable channel, as responsible for alcohol-induced elevation of intracellular Ca²⁺, intestinal barrier dysfunction, and systemic inflammation. Ethanol and acetaldehyde elicit TRPV6 ionic currents in Caco-2 cells. Studies in Caco-2 cell monolayers and mouse intestinal organoids show that TRPV6 deficiency or inhibition attenuates ethanol- and acetaldehyde-induced Ca²⁺ influx, tight junction disruption, and barrier dysfunction. Moreover, Trpv6^-/- mice are resist

SUBMITTER: Meena AS 

PROVIDER: S-EPMC9250449 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature